EP0420021A2 - Membranes poreuses hydrophiles et laminées, et méthodes pour leur préparation - Google Patents

Membranes poreuses hydrophiles et laminées, et méthodes pour leur préparation Download PDF

Info

Publication number
EP0420021A2
EP0420021A2 EP90118019A EP90118019A EP0420021A2 EP 0420021 A2 EP0420021 A2 EP 0420021A2 EP 90118019 A EP90118019 A EP 90118019A EP 90118019 A EP90118019 A EP 90118019A EP 0420021 A2 EP0420021 A2 EP 0420021A2
Authority
EP
European Patent Office
Prior art keywords
membrane
adhesive
laminated
membranes
surfactant
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP90118019A
Other languages
German (de)
English (en)
Other versions
EP0420021A3 (en
EP0420021B1 (fr
Inventor
Shan Fun Ching
Julian Gordon
Tsung-Hui K. Jou
Donald Irvine Stimpson
Dorothy Zakula
Peter Zaun
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott Laboratories
Original Assignee
Abbott Laboratories
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbott Laboratories filed Critical Abbott Laboratories
Publication of EP0420021A2 publication Critical patent/EP0420021A2/fr
Publication of EP0420021A3 publication Critical patent/EP0420021A3/en
Application granted granted Critical
Publication of EP0420021B1 publication Critical patent/EP0420021B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/545—Synthetic resin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/548—Carbohydrates, e.g. dextran
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody

Definitions

  • This invention relates to porous membranes useful in immunochromatographic assay devices and, in particular, to laminated nitrocellulose membranes in which hydrophobicity is avoided.
  • the application is related to two co-owned and concurrently filed applications bearing the same title.
  • the co-pending applications are Serial No. , (Attorney Docket No. 4719) and Serial No. , (Attorney Docket No. 4720).
  • Porous membranes particularly nitrocellulose membranes, have been used in biochemical procedures such as purification, analytical methodology, and in immunodiagnostics.
  • the well known Western blot is but one example.
  • Nitrocellulose membranes have also been used in immunochromatographic assays such as that disclosed in EP-A-299,428 (Abbott Laboratories).
  • nitrocellulose membranes are their weak mechanical strength.
  • Another problem associated with chromatographic membranes is evaporation of fluids during the course of chromatography.
  • nitrocellulose membranes may be laminated to a support material such as MylarTM.
  • MylarTM a support material
  • the adhesives used in such laminations often affect the hydrophilic properties of the nitrocellulose and render them unstable over time. It has been found that several adhesives used in the lamination of nitrocellulose membranes cause decreased hydrophilicity, as measured by decreasing capillary flow rates through the pores of the membranes.
  • the invention relates to a solid phase apparatus useful in a diagnostic assay, comprising a porous wettable membrane with which a biologically active reagent is contacted, said membrane being laminated on at least one side to a support using a water solvent based adhesive, the biologically active reagent retaining its activity.
  • the porous membrane comprises nitrocellulose and the adhesive comprises Adhesive Research AS73.
  • the membrane may incorporate a surfactant, preferably an alkyl sulfate or an alkyl sulfonic acid, the alkyl chain having from 1 to about 12 carbon atoms.
  • the apparatus may be laminated on one or both sides of the membrane, using a water solvent based adhesive.
  • the invention encompasses a process for preparing a laminated, wettable solid phase support useful in a diagnostic assay for determining the presence or amount of an analyte, the process comprising:
  • the preferred membrane and surfactants are as before.
  • the preferred support comprises a semi-rigid polyester or polyolefin plastic.
  • the method may include a step of laminating the opposite side of the porous membrane using a water solvent based adhesive.
  • the biologically active reagent is an enzyme or a binding partner, such as antibody or nucleic acid.
  • the invention is a method for determining the presence or amount of a ligand-analyte in a sample using a porous, wettable membrane solid phase, comprising:
  • the preferred membrane and surfactant are as before.
  • one side only is laminated and the localized site is contacted with sample by immersing the membrane with sample.
  • the localized site is contacted by contacting one end of the membrane with sample and allowing sample to wick through the membrane to contact the localized site.
  • the membrane may be laminated on both sides.
  • ligand-ligand receptor complex is detected by contact with a tracer capable of generating a detectable signal.
  • the signal may be directly detectable,as with colloidal or isotopic conjugates, or indirectly detectable using enzyme conjugates.
  • the signal may be visual color, chemiluminescence, or fluorescence.
  • FIG. 1 depicts an exemplary embodiment of the invention.
  • An improved porous membrane (10) is laminated on at least one side to a support (14).
  • the membrane (10) is held to the support (14) by an adhesive layer (12).
  • Porous membranes according to the invention have surfactants incorporated into them, which render the membranes wettable yet do not destroy the activity of biologically active reagents in contact therewith.
  • Bioly active reagents include enzymes, nucleic acids and other proteins having activity in their native form. Since the reagent of the preferred embodiment is typically a protein, the term “protein” is often used herein in place of biologically active reagent. However, the invention is not limited to proteins. Similarly, the protein may be immobilized to the membrane or it may merely be in contact with it. It is important that the reagent retain is natural activity while in contact with the membrane and surfactants present there.
  • Porous membranes of the present invention are useful in a number of biochemical procedures in which proteins must be in contact with or immobilized to a solid phase which is then contacted with a fluid sample.
  • the membrane is laminated on only one side, the protein is applied to a localized site (15) on the surface of the opposite side and fluid is contacted from the opposite side.
  • Dot blots See EP-A-063 810) are exemplary of this type of procedure.
  • the membrane is ultimately laminated on both sides and fluids flow lengthwise through the membrane as in thin layer chromatography.
  • a membrane (10) is laminated on one side, protein is immobilized on a localized site (not shown) on the membrane and a second laminate, consisting of a second support (16) and an adhesive layer (15), is applied to the opposite side.
  • a second laminate consisting of a second support (16) and an adhesive layer (15) is applied to the opposite side.
  • hydrophilicity is here measured as the rate at which the solvent front traverses the membrane strips.
  • Darcy's law provides a rate by relating the distance the front travels to the time t.
  • L the relevant measurement is the time taken for the front to reach L.
  • a relative measure of hydrophilicity is given by comparing the time or "wicking" rate of treated laminated membranes against the time or wicking rate of untreated laminated membranes.
  • a membrane is considered "hydrophilic" if the flow rate is such that the front traverses a length compatible with visualizing a result (ie., 2 - 10 cm) in a time consistent with rapid diagnostic assays, (ie., less than 10 minutes and preferably less than 5 minutes).
  • the ability of the membrane to bind protein is important to this invention. Untreated membranes bind protein, presumably via hydrophobic residues of the protein and possibly through ionic or hydrogen interactions between the protein and the membranes. (Nitrocellulose is known to have a partial negative charge due to the nitrate groups.)
  • the relative ability of a membrane to bind protein can be determined by a number of immunological methods employing antibody as the protein, and determining the relative strength of the signal from a known, constant amount of analyte.
  • Protein can be contacted with membranes by a number of methods including but not limited to drying, crosslinking, covalent attachment and adsorption. It can be applied from pipette or, more preferably, it can be jetted onto/into a localized site of the membrane prior to lamination. It may be immobilized or move with the solvent front, so long as its activity is retained.
  • porous membrane is meant a variety of membranous materials having pores through which fluids can flow by capillary action.
  • exemplary membranes include nitrocellulose, sintered plastics such as sintered polyethylene or polypropylene, and polyvinylidene difluoride (PVDF).
  • the porous membranes are available in variety of pore sizes ranging from about 0.4 micrometer (“um” or “micron”) to about 10 um. Larger pore sizes (i.e. 5 um) are presently preferred for immunodiagnostics because they provide higher fluid flow rates, which lead to more rapidly performed assays.
  • a preferred porous membrane is nitrocellulose.
  • Nitrocellulose membranes are commercially available from a number of sources, including Gelman Sciences, Ann Arbor, MI; Milliporel Bedford, MA; Schleicher and Schuell (S & S), Keene, NH; Sartorius GmbH, Gottingen, W. Germany; and Micron Separations, Inc. (MSI), Westborough, MA. These commercial sources of nitrocellulose produce membranes having pore sizes from 0.45 um to about 5 um. commercially, available nitrocellulose membranes may incorporate proprietary surfactants as discussed below.
  • PVDF membranes are available from Millipore. They too are available in several pore sizes, ranging from about 0.22 to about 2.0 um, although other pore sizes may become available. PVDF is generally more hydrophobic than nitrocellulose. As a result, it may bind proteins more tightly, but typically is less wettable and provides poor wicking rates. A hydrophilized product, Durapore, is available from Millipore in a variety of pore size ranges.
  • laminate or “membrane laminate” shall refer to a membrane bonded to a support.
  • laminate or “laminae” shall refer to the support layer to which the membrane is bonded, and may include an associated adhesive layer and a protective release liner.
  • One method of making membrane laminates involves heat sensitive laminae such as MonokoteTM, available from Top Flight, Chicago, IL. With this particular product, the membrane is laid adjacent the support and heat is applied to the surface to bond the two layers together. This method has the advantage that no additional surfactant is required to maintain the hydrophilicity of the membrane. It remains stable over a reasonable storage time. However, it is not presently a preferred method since the application of heat may inactivate protein already bound to the membrane. In addition, the manufacturing process is facilitated if pressure sensitive laminae are employed. Pressure sensitive laminae adhere to membranes upon the application of pressure.
  • Laminae useful with the present invention include polyesters such as MylarTM, polyolefins and similar plastics having comparable tensile strength.
  • the support lamina is used to give the porous membranes additional mechanical strength and to deter evaporation.
  • typical laminae provide a support layer (14) coated with a layer of adhesive material (12) which, in turn, is covered by a release liner (20).
  • the release liner is paper, polyester or similar material having a coating of silicone or other similar material which prevents the adhesive from binding securely to the release liner.
  • "Transfer adhesives" are available having an adhesive layer sandwiched between two release liners. These can be used for special applications where a separate support layer is undesirable.
  • Polyester support laminae having a support thickness of 50 to 200 mils, preferably 100 to 150 mils are presently preferred due to their ready availability.
  • such laminae are available from Flexcon, Spencer, MA, and Adhesive Research, Inc., Glenrock, PA.
  • an adhesive compound is generally coated onto one surface of a release liner and dried in an oven. The dried adhesive is then contacted with the support layer to form a support lamina.
  • Adhesives are described in Shields, J., Adhesive Handbook , 3rd Ed., (rev. 1985) and typically comprise an adhesive compound combined with tackifiers in a solvent.
  • Adhesive compounds include acrylics, such as polymethylmethacrylate, rubbers and silicones among others. Other adhesive polymers and tackifiers are known to those of ordinary skill in the adhesive arts.
  • the solvent may be organic based or water based.
  • the Flexcon adhesive V23 shown in Table I is an organic solvent based (OSB) adhesive, as are Flexcon V95 and V170, and 3M #396.
  • Adhesive Research, Inc (AR) adhesive AS73 e.g. product No. 7279
  • casein polyvinyl acetate
  • PVP polyvinylpyrrolidone
  • compositions of commercially available adhesives are frequently not disclosed by laminae manufactures, the invention can be practiced by using the readily available adhesives referred to herein, which can be ordered by number from the designated manufacturers. Nevertheless, the scope of the invention is not limited to any particular adhesive described herein.
  • WSB adhesives Although the release of water from the WSB adhesives would not have this detrimental effect on the membranes, it was believed that WSB adhesives would dissolve upon contact with aqueous samples, thereby causing delamination and destruction of the laminated apparatus. Surprisingly, it was found that WSB adhesives can be employed successfully without degradation of the membrane laminate.
  • the adhesive contained in the heat sensitive MonokoteTM product also was stable with most nitrocellulose brands tested.
  • WSB adhesives generally form laminates that are stable with commercially available "off-the-shelf" nitrocellulose membranes.
  • OSB adhesives it was desirable to find a way to treat the commercially available nitrocellulose so that more brands remain stably wettable upon lamination and so that more brands retained the ability to bind proteins.
  • surfactants which could be added to the nitrocellulose to prevent it from becoming hydrophobic upon lamination with OSB adhesives.
  • the vehicle from which the surfactant is applied to the membrane may also affect its ability to improve the stability of the membranes. While not all surfactants are soluble in all vehicles, as a general rule, surfactants which were applied from a water vehicle performed better than surfactants applied from an isopropanol vehicle.
  • a nonexclusive list of surfactants is given in Table II. They are characterized as non-ionic, cationic, anionic, zwitterionic or antistatic agents. Also given in Table II is the vehicle from which the surfactant was applied and the success of the surfactant as measured by its ability to prevent the membrane from becoming hydrophobic over time while retaining the ability of the membrane to bind proteins. The result is scored a "+" only if the resulting membrane gave good protein activity signal and maintained stable wicking rates over time (taken as indicative of retaining hydrophilicity). The data from Table II is also discussed further in the Examples which follow.
  • the first class is the anionic surfactants applied from a water vehicle.
  • the anionics consist of a negatively charged polar headed to a non-polar tail.
  • the polar heads typically comprise a sulfate, sulfonic acid, phosphate, or carboxylate group.
  • the non-polar tails comprise hydrocarbon chains having anywhere from 1 to about 16 carbons.
  • the tails may be branched or straight and may also contain other non-polar substituents.
  • Preferably the tail length is 1 to about 12 carbons; most preferably, from 1 to about 8 carbons.
  • Anionic surfactants are commercially available from numerous sources, typically as the sodium or potassium salt.
  • Preferred anionics include alkyl sulfates and alkyl sulfonic acids having from 1-8 carbon atoms.
  • Cyastat-like consists of a non-polar chain R1 attached to a trimethylammonium cationic head, coupled with a polar anion bonded to a lower alkyl group R2.
  • R1 comprises a straight or branched side chain having from 8 to about 20 carbons.
  • R1 may, also include other substituents, such as the amido moiety of Cyastat LS.
  • R2 represents a straight or branched alkyl side chain having from 1 to about 5 carbons.
  • the polar anion may be any of the anions possible with anionic surfactants (see above), although sulfate is presently preferred.
  • the concentration of surfactant used varies from 0.01% to about 10% (w/w) depending on the particular surfactant.
  • anionic surfactants are preferably used in concentrations of 0.1% to about 8% (w/w); most preferably from about 0.25% to about 3.5% (w/w). Since PVDF is more hydrophobic to begin with, slightly higher treatment concentrations (w/v) are preferred but are partially offset by the reduced conversion factor.
  • the final preferred concentrations range from about 1.0% to about 10% (w/w); most preferrably from about 2% to about 5% (w/w).
  • the Cyastat-like agents are preferably used in a concentration range of from about 0.01% to about 10% (w/w), depending on the membrane.
  • the preferred concentration of these agents is from about 0.1% to about 2.0% (w/w); most preferably from about 0.2% to about 0.5% (w/w).
  • the preferred concentrations range from about 2% to about 10% (w/w); most preferably from about 5% to about 9% (w/w).
  • the final concentration (w/w) can be obtained from the treatment solution concentration (w/v) by the constant conversion factor as taught in the note following Table I.
  • the final membranes tested included whatever proprietary surfactants the particular membrane manufacturer includes, less as much of that surfactant as may have been lost by treatment with additional surfactants in the hands of the inventors. Therefore, the claimed surfactant concentrations given as (%w/w) for anionics include from about 0.01 - to about 3% allowances for anionic surfactants that may have been added to the membranes by the manufacturer.
  • Surfactant can be incorporated into the membranes after lamination (of one side) but it is preferable to incorporate surfactant prior to lamination.
  • the opposite side of a membrane can also be laminated according to a similar procedure.
  • any protein to be applied must be done before the second lamination. Since the protein is applied to the surface of the membrane, protein stability problems associated with lamination would be expected to be greatest in the second lamination operation of the same membrane.
  • both, sides of an immunochromatographic strip can be laminated. This has the added advantage of keeping contaminants out and inhibiting evaporation of sample fluids.
  • a small section (about 1/4 inch) at one end is typically left unlaminated for contact with adjacent members or zones.
  • Nitrocellulose membrane 5 micron pore size from Schleicher & Schuell, was laminated on both sides using a solvent based acrylic adhesive tape from Flexcon (PM100CM/V23/71PMO) and stored at 22, 37 and 45° C.
  • a solvent based acrylic adhesive tape from Flexcon (PM100CM/V23/71PMO)
  • the hydrophilicity of the membrane was tested by immersing a strip of laminated membrane 1-3 mm into a test solution (0.1M Tris pH 7.4, 0.9% NaCl, phenol red) and measuring the time required for the solution front to migrate a distance of 5.4 cm. A more hydrophilic membrane requires a shorter time for the liquid to move 5.4 cm. Results (see Fig. 4) indicated that all the laminated membranes became less hydrophilic with time and that increasing the temperature of storage increased the rate at which loss of hydrophilicity occurred.
  • Nitrocellulose membrane (as in example 1) was laminated on both sides with solvent based acrylic adhesive (V23) tapes from Flexcon, PM100CM/V23/71PMO and PM150C/V23/Poly SC9, and a water based acrylic adhesive (AS73) tape from Adhesive Research, AR7279/AS73.
  • V23 solvent based acrylic adhesive
  • AS73 water based acrylic adhesive
  • a major difference between the two Flexcon tapes is that the release liner 71PMO is a paper release liner and Poly SC9 is a polyester release liner.
  • AR 7279/AS73 has a polyester release liner.
  • the membranes were incubated at 37° C and tested as described in example 1. Wicking Time (min) to traverse 5.4 cm strip After specified No.
  • Membrane laminated with AR 7279/AS73 did not become less hydrophilic after 168 days; membrane laminated with PM100CM/V23/71PMO became less hydrophilic by a factor of about two after 140 days; membrane laminated with PM150C/V23/Poly SC9 suffered the greatest loss of hydrophilic character which was a factor of 2.7 after only 35 days.
  • the data indicates that solvent based adhesives can cause the laminated membrane to become hydrophobic.
  • the release liner may play a role in this system by affecting the amount of solvent remaining in the adhesive layer at time of use. One would expect more solvent to be retained in the adhesive with the impermeable polyester release liner Poly SC9 than in the permeable paper liner 71PMO.
  • membrane can be laminated using water based adhesives without loss of the desired hydrophilic character.
  • Nitrocellulose membrane was laminated and tested as described in example 1 using Flexcon PM150C/V23/Poly SC9 solvent based acrylic adhesive tape. The results indicated that lamination of membrane with this material followed by incubation at 45° C. caused the greatest loss of hydrophilic character. Wicking Time (min) to traverse 5.4 cm strip After specified No. of Days Storage at 45° C: Adhesive 0 7 14 21 28 56 84 112 140 168 Flexcon 71PMO 4.1 5.9 6.5 6.6 7.2 8.2 8.9 9.2 11.5 11.9 Flexcon Poly SC9 3.6 10.0 10.4 12.6 12.3
  • Nitrocellulose membrane was impregnated with a single surfactant (see below) by dipping the membrane in a solution of the surfactant such that the membrane was completely wetted by the solution.
  • the membrane was removed from the solution after 5-10 seconds, suspended by a paper clip and allowed to dry at room temperature conditions for 2-20 hours.
  • the resulting membrane was tested as follows. A solution of anti-HCG antibody at 1.2 mg/ml was applied to the membrane in a narrow zone by pumping the solution through a fine capillary tube (Micro ML Tubing, Elmhurst, NY) at a flow rate of 0.05 ml/minute and moving the tubing across the membrane surface at a rate of 0.5 inches/second. The antibody immobilized on the membrane in this narrow zone forms the capture site.
  • a fine capillary tube Micro ML Tubing, Elmhurst, NY
  • the membrane was cut into strips and immunochromatography carried out with a selenium conjugate which binds HCG (see eg. EP-A-299 428).
  • the effect of each surfactant on antibody binding to the membrane was evaluated by the relative amount of selenium conjugate bound to the capture site when 50 mIU HCG urine was used for immunochromatography. Reduction of signal in this test was interpreted as a loss of nitrocellulose antibody binding capacity caused by a blocking effect of the surfactant.
  • Nitrocellulose membrane was treated and tested as described above with each of the following surfactants (from water unless specified otherwise) at a concentration of 1% w/v: Triton X100, Triton X405, Pluronic F68, Pluronic L62F, Pluronic L101, Tween 80, Tween 20, Brij 351 Mackanate DC30, CHAPS, and dioctyl sulfosuccinate (from isopropanol).
  • the surfactant treated membrane resulted in a loss of signal development during immunochromatography.
  • Nitrocellulose membrane was treated and tested as described above with each of the following surfactants (from isopropanol) at a concentration of 0.1% w/v: Mackanate DC30, cetyl alcohol, Zonyl FSO, Zonyl FSN, Zonyl FSP, Zonyl FSJ, and Pluronic L101.
  • Membranes treated with these surfactants showed no reduction in signal development during immunochromatography, however, the membrane wicking rate decreased as a result of the treatment (which is taken to mean the membranes became less hydrophilic as discussed above).
  • Nitrocellulose membrane was treated and tested as described in Part B above, however, 0.5% glycerol was added to the surfactant solution to increase the capillary wicking rate. The resulting membranes showed no decrease in signal development during immunochromatography. (But see example 5 as to effect on hydrophilicity.)
  • Nitrocellulose membrane was treated and tested as described above with each of the following surfactants from an isopropanol solution at a concentration of 1% w/v: dodecyltrimethylammonium bromide, cetyltrimethylethylammonium bromide, hexadecyltrimethylammonium bromide, and Surfonyl 104PA.
  • the resulting membranes showed no decrease in signal development during immunochromatography. (But see example 5 as to effect on hydrophilicity.)
  • Nitrocellulose membrane was treated and tested as described above with each of the following surfactants (in water solution): 1% pentane sulfonic acid, 1% heptane sulfonic acid, 1%, octane sulfonic acid, 1% decane sulfonic acid, 0.1% dodecane sulfonic acid, 0.1% sodium dodecyl sulfate, and 0.2% Cyastat LS. The resulting membranes showed no decrease in signal development during immunochromatography.
  • Nitrocellulose membrane was treated and tested as described in example 4, Part E with 1% Cyastat LS in either isopropanol or water solutionl and subsequently tested as described in example 3.
  • the membrane treated from the isopropanol solution lost hydrophilic character upon lamination and aging with PM150C/V23/Poly SC9, whereas the membrane treated from the water solution did not.
  • Nitrocellulose membrane (S&S 5 micron) was laminated with an organic solvent rubber based adhesive (3M-#396), stored at 370° C and tested for capillary wicking rate. Wicking Time (min) to traverse 5.4 cm strip After specified No. of Days Storage: Adhesive 0 7 14 21 28 3M #396 4.7 22.2 26.3 33.3 37.7
  • Nitrocellulose membrane was laminated with an organic solvent acrylic based adhesive (Flexcon V95), stored at 37° C and tested for capillary wicking rate. Wicking Time (min) to traverse 5.4 cm strip After specified No. of Days Storage: Adhesive 0 7 14 21 Flexcon V-95 5.0 8.7 9.3 10.3
  • Nitrocellulose membrane was laminated with an organic solvent acrylic based adhesive (Flexcon V170), stored at 37° C and tested for capillary wicking rate. Wicking Time (min) to traverse 5.4 cm strip After specified No. of Days Storage: Adhesive 0 7 14 21 28 56 84 112 140 Flexcon V170 4.2 6.2 7.1 9.1 7.3 8.9 10.0 9.7 11.9
  • Nitrocellulose membrane was laminated with a heat activated adhesive (MonoKote), stored at 37° C and tested for capillary wicking rate. Wicking Time (min) to traverse 5.4 cm strip After specified No. of Days Storage: Adhesive 0 7 14 21 Monokote 4.1 4.2 4.4 4.5
  • Nitrocellulose is laminated with a hot-melt adhesive consisting of a layer of polyethylene bonded to polyester.
  • the hot-melt adhesive is a thermoplastic of 100% solids with a melt temperature ranging from 65-90° C. This lamination process should not affect membrane flow rate because their is no opportunity for hydrophobic, organic solvents to migrate from the bonding layer into the membrane.
  • Nitrocellulose is laminated with a water based casein adhesive consisting of a layer of viscous casein solution bonded to a polyester support.
  • a water based casein adhesive consisting of a layer of viscous casein solution bonded to a polyester support.
  • Such a material is produced by applying a thin layer of a 20% solution of casein in water to polyester and evaporating water from the layer to reach a final concentration of 70-90%.
  • Lamination with this adhesive material should not cause a loss of hydrophillic character in the membrane because migration of water from the adhesive to the membrane would increase the degree of membrane hydration.
  • Nitrocellulose is laminated with a water based polyvinylpyrrolidone (PVP) adhesive consisting of a viscous PVP solution bonded to a polyester support.
  • PVP polyvinylpyrrolidone
  • Such a material is produced by applying a thin layer of 20-30% w/v PVP (molecular weight 3,000-5,000) and evaporating water from the layer to reach a final concentration of 70-90% w/v. Lamination with this material should not cause loss of hydrophilic character for reasons given in example 13.
  • Nitrocellulose is laminated with an adhesive made from a water emulsion of polyvinyl acetate (PVA) particles.
  • PVA polyvinyl acetate
  • a 70% solids water solution of PVA particles, 1-50 micron diameter, with 0.5% sodium dodecyl sulfate stabilizing surfactant is applied in a thin layer to a polyester support and the water evaporated to a final concentration of 90-99% solids. Lamination with this material should not cause loss of hydrophilic character for reasons given in example 13.
  • a nitrocellulose web 7.3 inches wide moving at 0.5 feet per minute was drawn through a bath of one of several solutions of Cyastat LS in concentrations as follows: 0.1, 0.2, 0.3, 0.4 and 0.5% (w/v).
  • the immersion path length was about 3-4 inches giving a resident time of 30-40 seconds.
  • the web was then dried in a drying tunnel at 60° C. for approximately 10 min. Strips cut from the sheet were tested as in examples 3 and 4 above using poly SC-9 laminates stored at 37° C. The signals from untreated control and 0.1% and 0.2% samples were good; the signals from 0.3% and 0.4% treated samples were fair; and the signal from the 0.5% treated sample was poor.
  • the hydrophilicity stability was as follows: Wicking Time (min) to traverse 5.4 cm strip After specified No.
  • PVDF Polyvinylidene difluoride
  • Hydrophobic PVDF membrane 2.0 micron was impregnated with a solution of 1% w/v Pluronic L101 and dried.
  • the resulting membrane could be wet by an aqueous solution of anti-HCG antibody, however, no signal was developed during 10 minutes of immunochromatography with anti-HCG selenium conjugate at a 500 mIU analyte concentration.
  • the surfactant allows wetting but blocks protein binding.
  • Hydrophobic PVDF membrane 2.0 micron was impregnated with a solution of 6.7% w/v Cyastat LS and dried. A 1 uL volume of anti-HCG antibody (3.3 mg/ml) was applied to the resulting membrane and immunochromatography carried out using anti-HCG selenium conjugate with 500 mIU HCG urine sample. Results showed signal development equivalent to that observed using nitrocellulose membrane.
  • PVDF membrane is dipped into isopropanol to obtain complete wetting of the material.
  • the isopropanol is washed out by soaking the wetted membrane in a water bath with several exchanges of the washing water
  • the membrane is then impregnated with sodium dodecyl sulfate (SDS) surfactant by dipping the membrane in a 5% w/v water solution of SDS for a sufficient time to allow diffusion of the surfactant into the void structure of the membrane.
  • SDS sodium dodecyl sulfate
  • the resulting membrane impregnated with the 5% water-SDS solution is removed from the bath and dried. Presuming the binding of protein to PVDF is similar to that of nitrocellulose, this membrane should easily wet and immobilize aqueous solutions of antibody.
  • This is a general means of introducing surfactants which are soluble in water but not soluble in organic solvents like isopropanol into a hydrophobic PVDF membrane.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Food Science & Technology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Laminated Bodies (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
EP90118019A 1989-09-27 1990-09-19 Membranes poreuses hydrophiles et laminées, et méthodes pour leur préparation Expired - Lifetime EP0420021B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41351989A 1989-09-27 1989-09-27
US413519 1995-03-30

Publications (3)

Publication Number Publication Date
EP0420021A2 true EP0420021A2 (fr) 1991-04-03
EP0420021A3 EP0420021A3 (en) 1991-12-18
EP0420021B1 EP0420021B1 (fr) 1996-07-17

Family

ID=23637532

Family Applications (1)

Application Number Title Priority Date Filing Date
EP90118019A Expired - Lifetime EP0420021B1 (fr) 1989-09-27 1990-09-19 Membranes poreuses hydrophiles et laminées, et méthodes pour leur préparation

Country Status (10)

Country Link
EP (1) EP0420021B1 (fr)
JP (1) JP2820785B2 (fr)
KR (1) KR0131317B1 (fr)
AT (1) ATE140537T1 (fr)
AU (1) AU630236B2 (fr)
CA (1) CA2025476A1 (fr)
DE (1) DE69027826T2 (fr)
DK (1) DK0420021T3 (fr)
ES (1) ES2091782T3 (fr)
GR (1) GR3020887T3 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996034738A2 (fr) * 1995-05-02 1996-11-07 Carter Wallace, Inc. Procede de fabrication d'un substrat stratifie et appareil de marquage du substrat avec un reactif
US5739041A (en) * 1995-05-02 1998-04-14 Carter Wallace, Inc. Diagnostic detection device
US6048735A (en) * 1996-12-05 2000-04-11 Idego Aps Sensor laminates and multi-sectioned fluid delivery devices for detecting by immunoassay target molecules in biological fluids
EP1003038A1 (fr) * 1997-07-28 2000-05-24 Dainabot Co., Ltd. Appareil de dosage immunologique
EP1084748A2 (fr) * 1999-09-17 2001-03-21 Fuji Photo Film Co., Ltd. Matériau adsorbant à base de biopolymère sous forme de membrane et kit adsorbant à base de biopolymère
WO2006013329A1 (fr) * 2004-08-06 2006-02-09 Inverness Medical Switzerland Gmbh Dispositif et methode d'essai
WO2009118423A1 (fr) * 2008-03-28 2009-10-01 Dentognostics Gmbh Dispositif d’absorption des protéines de fluides corporels
US8968198B2 (en) 2006-02-22 2015-03-03 Dexcom, Inc. Analyte sensor
EP2418488B1 (fr) 2009-04-09 2015-08-12 ARKRAY, Inc. Outil d'analyse d'echantillons, procede de fabrication d'outil d'analyse d'echantillons, et procede pour minimiser la baisse dans la permeabilite de solution d'organe de deploiement
US10524703B2 (en) 2004-07-13 2020-01-07 Dexcom, Inc. Transcutaneous analyte sensor
US10610137B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10813577B2 (en) 2005-06-21 2020-10-27 Dexcom, Inc. Analyte sensor
EP4180117A1 (fr) * 2021-11-16 2023-05-17 Sartorius Stedim Biotech GmbH Membrane d'analyse microbiologique

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2684488A (en) 1988-06-27 1990-01-04 Carter-Wallace, Inc. Test device and method for colored particle immunoassay
US6319676B1 (en) 1995-05-02 2001-11-20 Carter Wallace, Inc. Diagnostic detection device and method
US5879951A (en) 1997-01-29 1999-03-09 Smithkline Diagnostics, Inc. Opposable-element assay device employing unidirectional flow
US5939252A (en) 1997-05-09 1999-08-17 Lennon; Donald J. Detachable-element assay device
CA2771000A1 (fr) * 1998-10-23 2000-05-04 Qiagen Gesellschaft Mit Beschraenkter Haftung Procedes et moyens pour l'isolement et la purification d'acides nucleiques sur des surfaces
JP4472823B2 (ja) * 2000-02-04 2010-06-02 パナソニック株式会社 クロマトグラフィー試験片、及びその製造方法
MX2010013964A (es) 2008-06-30 2011-05-02 Sekisui Medical Co Ltd Fase solida porosa para ensayo de union, y metodo de ensayo de union que utiliza la misma.
JP6918811B2 (ja) 2015-10-21 2021-08-11 パウア・トレーディング・リミテッドＰａｕａ Ｔｒａｄｉｎｇ Ｌｉｍｉｔｅｄ 物品を入れるための持ち運び可能なケース、およびそれを製造するための方法
MA48458A (fr) 2017-04-27 2020-03-04 Paua Trading Ltd Étui ou housse de protection

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0174247A2 (fr) * 1984-08-23 1986-03-12 Bernard Guerin Bandelette d'analyse immunologique et procédé pour sa fabrication
EP0175195A2 (fr) * 1984-09-13 1986-03-26 BEHRINGWERKE Aktiengesellschaft Un dispositif comportant des polymères à structure de membrane et particules solides incorporées
EP0212599A2 (fr) * 1985-08-28 1987-03-04 Miles Inc. Elément analytique multicouche pour des essais immunologiques ayant une couche pour concentrer le signal détectable
EP0274911A1 (fr) * 1987-01-12 1988-07-20 Pall Corporation Moyen de diagnostic, sa préparation et son utilisation
EP0284232A1 (fr) * 1987-03-27 1988-09-28 Becton, Dickinson and Company Essai en phase solide
EP0291176A1 (fr) * 1987-05-13 1988-11-17 Becton, Dickinson and Company Essai en phase solide employant l'écoulement capillaire

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1504921A (fr) * 1966-12-07 1967-12-08 Random & Imain Tissu collant et procédé pour sa fabrication
EP0063810B1 (fr) * 1981-04-29 1986-03-05 Ciba-Geigy Ag Dispositif et trousses pour les analyses immunologiques
EP0254202B1 (fr) * 1986-07-15 1991-09-18 Fuji Photo Film Co., Ltd. Méthode de production d'un dispositif d'analyse multi-couche intégrant
JPS63206658A (ja) * 1987-02-23 1988-08-25 Agency Of Ind Science & Technol タンパク質の高感度検出法
US5006464A (en) * 1987-10-01 1991-04-09 E-Y Laboratories, Inc. Directed flow diagnostic device and method
JPH02107649A (ja) * 1988-10-18 1990-04-19 Asahi Glass Co Ltd 親水性多孔膜の製造法
JPH02218957A (ja) * 1989-02-20 1990-08-31 Fuji Photo Film Co Ltd 全血試料分析用多層分析要素
DE3922495A1 (de) * 1989-07-08 1991-01-17 Miles Inc Analyseverfahren fuer substanzen aus biologischen fluessigkeiten, insbesondere vollblut

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0174247A2 (fr) * 1984-08-23 1986-03-12 Bernard Guerin Bandelette d'analyse immunologique et procédé pour sa fabrication
EP0175195A2 (fr) * 1984-09-13 1986-03-26 BEHRINGWERKE Aktiengesellschaft Un dispositif comportant des polymères à structure de membrane et particules solides incorporées
EP0212599A2 (fr) * 1985-08-28 1987-03-04 Miles Inc. Elément analytique multicouche pour des essais immunologiques ayant une couche pour concentrer le signal détectable
EP0274911A1 (fr) * 1987-01-12 1988-07-20 Pall Corporation Moyen de diagnostic, sa préparation et son utilisation
EP0284232A1 (fr) * 1987-03-27 1988-09-28 Becton, Dickinson and Company Essai en phase solide
EP0291176A1 (fr) * 1987-05-13 1988-11-17 Becton, Dickinson and Company Essai en phase solide employant l'écoulement capillaire

Cited By (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996034738A2 (fr) * 1995-05-02 1996-11-07 Carter Wallace, Inc. Procede de fabrication d'un substrat stratifie et appareil de marquage du substrat avec un reactif
WO1996034738A3 (fr) * 1995-05-02 1997-02-06 Carter Wallace Procede de fabrication d'un substrat stratifie et appareil de marquage du substrat avec un reactif
US5739041A (en) * 1995-05-02 1998-04-14 Carter Wallace, Inc. Diagnostic detection device
US5846835A (en) * 1995-05-02 1998-12-08 Carter Wallace, Inc. Manufacturing method for laminated immunodiagnostic test device
US6048735A (en) * 1996-12-05 2000-04-11 Idego Aps Sensor laminates and multi-sectioned fluid delivery devices for detecting by immunoassay target molecules in biological fluids
EP1003038A1 (fr) * 1997-07-28 2000-05-24 Dainabot Co., Ltd. Appareil de dosage immunologique
EP1003038A4 (fr) * 1997-07-28 2002-09-04 Dainabot Co Ltd Appareil de dosage immunologique
US6537828B1 (en) 1997-07-28 2003-03-25 Dainabot Co., Ltd. Immunoassay apparatus
EP1084748A2 (fr) * 1999-09-17 2001-03-21 Fuji Photo Film Co., Ltd. Matériau adsorbant à base de biopolymère sous forme de membrane et kit adsorbant à base de biopolymère
EP1084748A3 (fr) * 1999-09-17 2002-06-19 Fuji Photo Film Co., Ltd. Matériau adsorbant à base de biopolymère sous forme de membrane et kit adsorbant à base de biopolymère
US11045120B2 (en) 2004-07-13 2021-06-29 Dexcom, Inc. Analyte sensor
US10918315B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US11883164B2 (en) 2004-07-13 2024-01-30 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US11064917B2 (en) 2004-07-13 2021-07-20 Dexcom, Inc. Analyte sensor
US10799159B2 (en) 2004-07-13 2020-10-13 Dexcom, Inc. Analyte sensor
US11026605B1 (en) 2004-07-13 2021-06-08 Dexcom, Inc. Analyte sensor
US10993642B2 (en) 2004-07-13 2021-05-04 Dexcom, Inc. Analyte sensor
US10993641B2 (en) 2004-07-13 2021-05-04 Dexcom, Inc. Analyte sensor
US10980452B2 (en) 2004-07-13 2021-04-20 Dexcom, Inc. Analyte sensor
US10524703B2 (en) 2004-07-13 2020-01-07 Dexcom, Inc. Transcutaneous analyte sensor
US10932700B2 (en) 2004-07-13 2021-03-02 Dexcom, Inc. Analyte sensor
US10799158B2 (en) 2004-07-13 2020-10-13 Dexcom, Inc. Analyte sensor
US10813576B2 (en) 2004-07-13 2020-10-27 Dexcom, Inc. Analyte sensor
US10918313B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US10918314B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US10709362B2 (en) 2004-07-13 2020-07-14 Dexcom, Inc. Analyte sensor
US10709363B2 (en) 2004-07-13 2020-07-14 Dexcom, Inc. Analyte sensor
US10827956B2 (en) 2004-07-13 2020-11-10 Dexcom, Inc. Analyte sensor
US10722152B2 (en) 2004-07-13 2020-07-28 Dexcom, Inc. Analyte sensor
WO2006013329A1 (fr) * 2004-08-06 2006-02-09 Inverness Medical Switzerland Gmbh Dispositif et methode d'essai
GB2431988A (en) * 2004-08-06 2007-05-09 Inverness Medical Switzerland Assay device & method
US10918318B2 (en) 2005-03-10 2021-02-16 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10610137B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US11051726B2 (en) 2005-03-10 2021-07-06 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10716498B2 (en) 2005-03-10 2020-07-21 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10856787B2 (en) 2005-03-10 2020-12-08 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10898114B2 (en) 2005-03-10 2021-01-26 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10709364B2 (en) 2005-03-10 2020-07-14 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10617336B2 (en) 2005-03-10 2020-04-14 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10918316B2 (en) 2005-03-10 2021-02-16 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10918317B2 (en) 2005-03-10 2021-02-16 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10610135B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10610136B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10925524B2 (en) 2005-03-10 2021-02-23 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10743801B2 (en) 2005-03-10 2020-08-18 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US11000213B2 (en) 2005-03-10 2021-05-11 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10813577B2 (en) 2005-06-21 2020-10-27 Dexcom, Inc. Analyte sensor
US9724028B2 (en) 2006-02-22 2017-08-08 Dexcom, Inc. Analyte sensor
US8968198B2 (en) 2006-02-22 2015-03-03 Dexcom, Inc. Analyte sensor
CN101977553B (zh) * 2008-03-28 2014-10-08 丹通格诺斯蒂科斯有限公司 用于吸收体液中蛋白的装置
CN101977553A (zh) * 2008-03-28 2011-02-16 丹通格诺斯蒂科斯有限公司 用于吸收体液中蛋白的装置
WO2009118423A1 (fr) * 2008-03-28 2009-10-01 Dentognostics Gmbh Dispositif d’absorption des protéines de fluides corporels
EP2418488B1 (fr) 2009-04-09 2015-08-12 ARKRAY, Inc. Outil d'analyse d'echantillons, procede de fabrication d'outil d'analyse d'echantillons, et procede pour minimiser la baisse dans la permeabilite de solution d'organe de deploiement
US9903864B2 (en) 2009-04-09 2018-02-27 Arkray, Inc. Sample analysis tool, method for producing sample analysis tool, and method for inhibiting decrease in liquid permeability of development member
EP4180117A1 (fr) * 2021-11-16 2023-05-17 Sartorius Stedim Biotech GmbH Membrane d'analyse microbiologique
WO2023088888A1 (fr) * 2021-11-16 2023-05-25 Sartorius Stedim Biotech Gbmh Membrane pour analyse microbiologique

Also Published As

Publication number Publication date
JPH03120468A (ja) 1991-05-22
EP0420021A3 (en) 1991-12-18
EP0420021B1 (fr) 1996-07-17
DE69027826D1 (de) 1996-08-22
KR0131317B1 (ko) 1998-04-11
KR910006727A (ko) 1991-04-29
DK0420021T3 (da) 1996-11-25
JP2820785B2 (ja) 1998-11-05
ES2091782T3 (es) 1996-11-16
CA2025476A1 (fr) 1991-03-28
AU6323490A (en) 1991-04-11
ATE140537T1 (de) 1996-08-15
AU630236B2 (en) 1992-10-22
GR3020887T3 (en) 1996-11-30
DE69027826T2 (de) 1997-02-13

Similar Documents

Publication Publication Date Title
EP0420021B1 (fr) Membranes poreuses hydrophiles et laminées, et méthodes pour leur préparation
EP0051183B2 (fr) Elément d'analyse à plusieurs couches
JP2504923B2 (ja) 免疫学的測定方法
EP0164194B1 (fr) Ruban chromatographique, méthode de préparation et instrument diagnostique utilisant ce ruban
US6106779A (en) Lysis chamber for use in an assay device
US5369007A (en) Microassay on a card
EP2306194B1 (fr) Solution de développement pour l'immunochromatographie, et procédé de mesure l'utilisant
CA1256383A (fr) Dispositifs de chromatographie a rives modifiees
JP3220486B2 (ja) 血液グルコース濃度用可視試験片
JP2541674B2 (ja) ２種類の生物親和性パ―トナ―の特異的結合反応によつて試料液を分析検査するための試験キヤリヤ―
EP0421234A2 (fr) Membranes hydrophiles, laminées et poreuses, et leur procédé de préparation
EP2251690B1 (fr) Essai d'immuno-dosage et kit
US4945205A (en) Chromatographic strip having non-compressed edges
EP0421235A2 (fr) Membranes hydrophiles, laminées et poreuses, et leur procédé de préparation
JP2020020724A (ja) イムノクロマト用試験片及びイムノクロマト検出キット
EP0134236B1 (fr) Procede, matrice poreuse et dispositif pour effectuer des reactions analytiques d'affinites biospecifiques
WO2017002882A1 (fr) Dispositif d'analyse chromatographique et procédé d'analyse chromatographique
JP6572404B2 (ja) クロマトグラフィー媒体用基材、クロマトグラフィー媒体及びイムノクロマトグラフ用ストリップ
WO2020105079A1 (fr) Éprouvette pour immunochromatographie et kit de détection immunochromatographique
JP3436269B2 (ja) イムノクロマト法用測定器具
JP2002350443A (ja) 免疫測定法
JP2001074738A (ja) 免疫クロマトグラフ法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI NL SE

PUAL Search report despatched

Free format text: ORIGINAL CODE: 0009013

AK Designated contracting states

Kind code of ref document: A3

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI NL SE

17P Request for examination filed

Effective date: 19920609

17Q First examination report despatched

Effective date: 19931207

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI NL SE

REF Corresponds to:

Ref document number: 140537

Country of ref document: AT

Date of ref document: 19960815

Kind code of ref document: T

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 19960725

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DK

Payment date: 19960729

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 19960730

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 19960808

Year of fee payment: 7

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 19960819

Year of fee payment: 7

REF Corresponds to:

Ref document number: 69027826

Country of ref document: DE

Date of ref document: 19960822

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 19960827

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 19960828

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 19960910

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 19960920

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: AT

Payment date: 19960924

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GR

Payment date: 19960927

Year of fee payment: 7

ITF It: translation for a ep patent filed

Owner name: MODIANO & ASSOCIATI S.R.L.

REG Reference to a national code

Ref country code: CH

Ref legal event code: NV

Representative=s name: A. BRAUN, BRAUN, HERITIER, ESCHMANN AG PATENTANWAE

Ref country code: GR

Ref legal event code: FG4A

Free format text: 3020887

ET Fr: translation filed
REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2091782

Country of ref document: ES

Kind code of ref document: T3

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970919

Ref country code: DK

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970919

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970919

REG Reference to a national code

Ref country code: DK

Ref legal event code: EBP

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970920

Ref country code: ES

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 19970920

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970930

Ref country code: GR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970930

Ref country code: FR

Free format text: THE PATENT HAS BEEN ANNULLED BY A DECISION OF A NATIONAL AUTHORITY

Effective date: 19970930

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970930

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19970930

BERE Be: lapsed

Owner name: ABBOTT LABORATORIES

Effective date: 19970930

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19980401

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 19970919

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

NLV4 Nl: lapsed or anulled due to non-payment of the annual fee

Effective date: 19980401

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19980603

EUG Se: european patent has lapsed

Ref document number: 90118019.0

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20010201

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES;WARNING: LAPSES OF ITALIAN PATENTS WITH EFFECTIVE DATE BEFORE 2007 MAY HAVE OCCURRED AT ANY TIME BEFORE 2007. THE CORRECT EFFECTIVE DATE MAY BE DIFFERENT FROM THE ONE RECORDED.

Effective date: 20050919